ABSTRACT Overall Per- and polyfluoroalkyl substances (PFAS) are emerging as a major public health problem in North Carolina (NC) and across the US. PFAS comprise a class of almost 5,000 known compounds. Their unique chemical properties have been harnessed to make consumer and industrial products more water, stain, and grease resistant; they are found in products as diverse as cosmetics and firefighting foams. Despite increasing evidence that they are found ubiquitously in the environment, there is a paucity of knowledge about their toxicity. For the few well-studied PFAS, associated health effects include cancer and toxicity to the liver, thyroid, and immune system; but human exposure levels, mechanisms of action, bioaccumulation, or effective remediation approaches remain unclear for the majority of PFAS. As a result of recent widespread detection in the environment and increasing evidence of human exposure we propose to establish a Superfund Research Program (SRP) Center for Environmental and Human Health Effects of PFAS. Several of these compounds are included on the Substance Priority List of the Agency for Toxic Substances and Disease Registry and are considered contaminants of emerging concern by the US Environmental Protection Agency. The long-term objective of our Center is to advance understanding about PFAS 1) environmental and human exposure in impacted areas, 2) toxicity and underlying mechanisms of thyroid and immune function, 3) bioaccumulation potential, and 4) remediation. To meet our objective we will employ a highly transdisciplinary approach that will integrate leaders in diverse fields (epidemiology, environmental science and engineering, biology, toxicology, immunology, data science, and advanced analytics) across two major NC Universities (NC State and East Carolina Universities); multiple levels of biological organization (biomolecule, pathway, cell, model organisms (periphyton, mayflies, zebrafish, mouse), and human populations); state-of-the-art analytical technologies; cutting-edge data science and management approaches; a recognized track record in interdisciplinary, environmental health science training; and well-established partnerships with government and community stakeholders. We aim to be a trusted resource for SRP stakeholders and impacted communities and to catalyze discovery of information that leads to prevention of PFAS exposure and protection of human health.